Evaluation of Radiation Pneumonitis in a Phase 2 Study of Consolidation Immunotherapy With Nivolumab and Ipilimumab or Nivolumab Alone Following Concurrent Chemoradiation Therapy for Unresectable Stage IIIA/IIIB Non-Small Cell Lung Cancer

Purpose: The addition of immunotherapy (IO) after concurrent chemoradiation therapy (CCRT) for unresectable non-small cell lung cancer (NSCLC) has become common practice in eligible patients. Approaches to further improve outcomes and reduce treatment-related toxicity for these patients are needed. This study evaluates the risk of radiation pneumonitis after CCRT and its correlation with the radiation dose distribution, IO regimen (nivolumab vs nivolumab plus ipilimumab), and patient demographics across BTCRC-LUN16-081. Methods and Materials: Patients with unresectable stage III NSCLC after completion of CCRT were enrolled in BTCRCLUN16-081, a randomized phase 2 trial to assess the efficacy and tolerability of consolidative nivolumab versus nivolumab plus ipilimumab for 6 months. Radiation dose parameters, patient demographics, and toxicity events were evaluated among Results: One hundred-five patients were enrolled into 2 treatment arms; 54 patients received nivolumab alone, and 51 patients received nivolumab plus ipilimumab. Of these, 104 patients had dose-volume histogram information available. Within this cohort, 65 patients (62.5%) had stage IIIA, and 39 patients (37.5%) had stage IIIB NSCLC disease, per the American Journal Committee on Cancer, seventh edition. During the study, 29 patients (27.9%) were diagnosed with grade 2 or greater pneumonitis. Using logistic regression and evaluating different cutoffs for percentage of normal lung volume receiving at least 20 gy (V20), patients with V20 > 23% demonstrated significantly fi cantly higher grade 2 or greater pneumonitis rates (37.1% vs 16.2%, P=.031). No significant fi cant difference in rates of pneumonitis between arms was identified. fi ed. Traditional lung dose -volume histo- gram cutoffs (percentage of normal lung volume receiving at least 5 gy (V5) > 65%, V20 > 35%, and mean > 20 Gy) were not associated with pneumonitis. Conclusions: In patients receiving nivolumab or nivolumab plus ipilimumab after definitive fi nitive CCRT, lung V20 > 23% was asso- ciated with an increased risk of grade 2 or greater pneumonitis. Radiation dose constraints for lungs in patients receiving con- solidative IO after CCRT should continue to be evaluated and optimized when feasible. (c) 2024 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.